Selective cell death of p53-insufficient cancer cells is induced by knockdown of the mRNA export molecule GANP

Suchada Phimsen, Kazuhiko Kuwahara, Teruo Nakaya, Kazutaka Ohta, Taiji Suda, Andri Rezano, Masahiro Kitabatake, Kulthida Vaeteewoottacharn, Seiji Okada, Shigenobu Tone, Nobuo Sakaguchi

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5 Citations (Scopus)

Abstract

Cancer cells often contain p53 abnormalities that impair cell-cycle checkpoint progression and cause resistance to various anti-cancer treatments. DNA damage occurs at actively transcribed genes during G1-phase in yeast cells that have a deficient mRNA export capacity. Here, we show that germinal center-associated nuclear protein (GANP), a homologue of yeast Sac3 that is involved in mRNA export, is indispensable for ensuring the stability of human genomic DNA and that GANP knockdown causes apoptosis and necrosis of p53-insufficient cancer cells. Ganp small interfering RNA (siGanp)-induced DNA damage, accompanied by a decrease in the number of cells in S-phase, caused late apoptosis and necrosis in p53-insufficient cancer cells through both caspase-dependent and -independent mechanisms. siGanp effectively induced DNA damage leading to cell death in p53-insufficient cancer cells in vitro and protect the growth of cancer cells transplanted into immunocompromized mice, suggesting that siGanp has potential as a selective treatment for p53-insufficient cancer cells.

Original languageEnglish
Pages (from-to)679-690
Number of pages12
JournalApoptosis
Volume17
Issue number7
DOIs
Publication statusPublished - 01-07-2012
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research

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    Phimsen, S., Kuwahara, K., Nakaya, T., Ohta, K., Suda, T., Rezano, A., Kitabatake, M., Vaeteewoottacharn, K., Okada, S., Tone, S., & Sakaguchi, N. (2012). Selective cell death of p53-insufficient cancer cells is induced by knockdown of the mRNA export molecule GANP. Apoptosis, 17(7), 679-690. https://doi.org/10.1007/s10495-012-0711-8